The long range goal of the proposed research is to understand the cellular basis of vision in normal and visually deprived animals. One objective is to study the connectivity of cells in the cat and monkey striate cortex by making intracellular recordings and marking cells, after having made a receptive field analysis, by iontophoretic injection of horseradish peroxidase (HRP). Neurons will be analyzed in terms of their interlaminar connectivity, 3-dimensional structure relative to the various systems of cortical columns, and their ultrastructure. The synaptic relationship between cells will also be studied through cross correlation analysis. A similar set of experiments will be carried out in monocularly deprived cats and monkeys. The connections between the striate cortex and other cortical areas will be studied to learn about the relationshp between the cortical projection bands and the ocular dominance and orientation columns. The effects of known putative neurotransmitters on cortical cells will be tested in in vivo and in vitro slice preparations. It is of special interest to determine the role of aspartate and glutamate, which may be the transmitters used by layer 6 cortical cells. A search will be made for new transmitter candidates, for which the cortical slice preparation will serve as a bioassay. Physiological and pharmacological studies will be carried out on dissociated visual cells in vitro. The work on solitary photoreceptors will be continued with special emphasis on the transduction mechanisms and adaptation. The identity and role of "internal transmitters" will be assessed in studies of solitary rods and cones from salamander retina. Other dissociated retinal cells from salamander of fish retinae will be studied under controlled experimental conditions. Special emphasis will be placed on the study of dissociated cells from the mammalian visual cortex, with the aim of learning about their physiological properties and chemical specificity. The formation of synapses in vitro will also be studied. Monoclonal antibodies will be developed toward retinal and cortical cells for identification of cell types in culture and during development. Fluorescence-labeled antibodies will be used as aids in separation of a given cell type but of a mixed population of dissociated cells through the used of a fluorescence activated cell sorter.